ArticleCancer research2023
The m6A Reader YTHDF2 Promotes Bladder Cancer Progression by Suppressing RIG-I-Mediated Immune Response.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 88 citations in OpenAlex.
- YTHDF2 drives malignant progression in cutaneous melanoma through m⁶A-dependent HMOX1-mediated ferroptosis.Medical oncology (Northwood, London, England) · 2026Article
- TET2 promotes monocyte inflammatory activation in asthma via ALKBH5-m6A regulation and PI3K signaling: evidence from m6A-SNP and single-cell analyses.Molecular genetics and genomics : MGG · 2026Article
- Screening of M6a methylated genes associated with preovulatory follicle development in Bashang long-tailed chicken.Poultry science · 2026Article
- N6-Methyladenosine RNA Methylation: A Key Regulator in Male Reproductive Disorders and Urological Cancers.The world journal of men's health · 2026Review
- m6A-modified circFOXA1 promotes tumor immune evasion via enhancing PD-L1 deubiquitination in triple-negative breast cancer.Cytotechnology · 2026Article
- mRedox biology · 2026Review
- YTHDF2 in inflammation: Mechanisms and therapeutic strategies.Genes & diseases · 2026Review
- Mechanisms and therapeutic potential of YTHDF readers: Linking epitranscriptomics to cancer.Journal of pharmaceutical analysis · 2026Review
- Targeting G9a Exerts Pleiotropic Suppression in Triple-Negative Breast Cancer Cells: Cooperatively Inducing Pyroptosis and Apoptosis.Biomolecules · 2026Article
- Zinc finger protein ZNF33B facilitates Japanese encephalitis virus replication by regulating mCell & bioscience · 2026Article
- mFrontiers in cell and developmental biology · 2026Review
- RNA methylation in urological cancers: regulatory logic, biological functions, and clinical relevance.Frontiers in immunology · 2026Review
- Determination of Nitrogen Metabolism-Related Prognostic Signatures for Forecasting Bladder Cancer PrognosisEndocrine, metabolic & immune disorders drug targets · 2026Article
- RNA epitranscriptomic regulation of tumor immune evasion: mechanisms, context-dependent roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Mechanisms of microbiome-immune interactions in bladder cancer and targeted regulatory strategies.Frontiers in immunology · 2026Review
- mFrontiers in immunology · 2026Article
- Fbxo2 suppresses prostate cancer progression by regulating YTHDF2 ubiquitination and degradation.Cell death & disease · 2025Article
- RNA modifications: roles in immune cell biology and tumor regulation.Cancer cell international · 2025Review
- Multifaceted functions of Y‑box binding protein 1 in RNA methylated modifications (Review).Molecular medicine reports · 2025Review
- METAP2 inhibits K48-linked ubiquitination of YTHDF2 to promote ovarian cancer progression.Oncogene · 2025Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N6-Methyladenosine (m6A) is the most prevalent internal modification of mammalian mRNAs. Recent studies have shown that m6A methyltransferases METTL3 and METTL14 play important roles in urothelial bladder carcinoma (BLCA). To provide a more comprehensive understanding of the m6A regulatory landscape in bladder cancer, we investigated the role of YTHDF2, a crucial m6A reader, in BLCA. YTHDF2 was frequently upregulated at both the RNA and protein level in BLCA. Functionally, YTHDF2 promoted the proliferation and tumor growth of BLCA cells in vitro and in vivo, respectively. Integrative RNA sequencing and m6A sequencing analyses identified RIG-I as a downstream target of YTHDF2. Mechanistically, YTHDF2 bound to the coding sequence of DDX58 mRNA, which encodes RIG-I, and mediated its degradation in an m6A-dependent manner. Knockdown of RIG-I inhibited apoptosis and promoted the proliferation of BLCA cells. Depleting RIG-I was also able to reverse the effects of YTHDF2 deficiency. YTHDF2-deficient BLCA cells implanted orthotopically in recipient mice activated an innate immune response and promoted recruitment of CD8+ T lymphocytes into the tumor bed and the urothelium. Moreover, YTHDF2 deficiency enhanced the efficacy of Bacillus Calmette-Guérin immunotherapy treatment. This study reveals that YTHDF2 acts as an oncogene in BLCA. YTHDF2 inhibits RIG-I to facilitate immune evasion, supporting testing YTHDF2 inhibition in combination with immunotherapy. SIGNIFICANCE: YTHDF2 regulates RIG-I-mediated innate immune signaling to support bladder cancer progression, highlighting the functional importance of m6A modifications in bladder cancer and uncovering therapeutic opportunities to improve patient outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.